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Biomedical subjects

L Ngo

Publications and source records attributed to L Ngo.

At least 37 records · Page 2Linked to original sources

Epidemiological health study of a town exposed to chemicals.

The purpose of this survey was to assess the health status of community residents exposed to a 16-day release of Catacarb from a nearby refinery and to document the prevalence rates of symptoms and illnesses of this town. The health status of the exposed residents was compared to that of unexposed residents of a demographically similar control town. An epidemiologic study design was used and questionnaires were mailed to all households in both towns. Response rate was 43%. Household cluster effects, gender, education, and race were controlled in the analysis. Questionnaire health data reveal increased reporting of symptoms in the exposed, specifically headaches, respiratory, visual, gastrointestinal, and dermatologic with odds ratios ranging between 1.3 and 3. Exposure relationships with increased symptoms and worsening of illnesses was found.

Adolescent↗

Efficient temporal probabilistic reasoning via context-sensitive model construction.

We present a language for representing context-sensitive temporal probabilistic knowledge. Context constraints allow inference to be focused on only the relevant portions of the probabilistic knowledge. We provide a declarative semantics for our language. We present a sound and complete algorithm for computing posterior probabilities of temporal queries, as well as an efficient implementation of the algorithm. Throughout we illustrate the approach with the problem of reasoning about the effects of medications and interventions on the state of a patient in cardiac arrest. We empirically evaluate the efficiency of our system by comparing its inference times on problems in this domain with those of standard Bayesian network representations of the problems.

Algorithms↗

Electrocardiographic and hemodynamic changes and their association with myocardial infarction during coronary artery bypass surgery. A multicenter study. Multicenter Study of Perioperative Ischemia (McSPI) Research Group.

BACKGROUND: Electrocardiographic (ECG) changes during coronary artery bypass graft surgery have not been described in detail in a large multicenter population. The authors describe these ECG changes and evaluate them, along with demographic and clinical characteristics and intraoperative hemodynamic alterations, as predictors of myocardial infarction (MI) as defined by two sets of criteria. METHODS: Data from 566 patients at 20 clinical sites, collected as part of a clinical trial to evaluate the efficacy of acadesine for reducing MI, were analyzed at core laboratories. Perioperative ECG changes were identified using continuous three-lead Holter ECG. Systolic blood pressure, diastolic blood pressure, and heart rate were recorded each minute during operation. The occurrence of MI by Q wave or myocardial fraction of creatine kinase (CK-MB) or autopsy criteria, and by (Q wave and CK-MB) or autopsy criteria was determined. RESULTS: During perioperative Holter monitoring, episodes of ST segment deviation, major cardiac conduction changes > or = 30 min, or use of ventricular pacing > or = 30 min occurred in 58% patients, primarily in the first 8 h after release of aortic occlusion. Of the 25% patients who met the Q wave or CK-MB or autopsy criteria for MI, 19% had increased CK-MB as well as ECG changes. (Q wave and CK-MB) or autopsy criteria for MI were met by 4% of patients. The CK-MB concentration generally peaked by 16 h after release of aortic occlusion. In patients with (n = 187) and without a perioperative episode of ST segment deviation, the incidence of MI was 36% and 19%, respectively (P < 0.01), by Q wave or CK-MB or autopsy criteria, and 6% and 3%, respectively (P = 0.055), by (Q wave and CK-MB) or autopsy criteria. Multiple logistic regression analysis showed that intraoperative ST segment deviation, intraventricular conduction defect, left bundle branch block, duration of hypotension (systolic blood pressure < 90 mmHg) after cardiopulmonary bypass, and duration of cardiopulmonary bypass are independent predictors of Q wave or CK-MB or autopsy MI. The independent predictors of (Q wave and CK-MB) or autopsy MI are intraoperative ST segment deviation and duration of aortic occlusion. CONCLUSIONS: Major ECG changes occurred in 58% of patients during coronary artery bypass graft surgery, primarily within 8 h after release of aortic occlusion. Multicenter data collection revealed a substantial variation in the incidence of MI and an overall incidence of up to 25%, with most MI occurring within 16 h after release of aortic occlusion. Intraoperative monitoring of ECG and hemodynamics has incremental value for predicting MI.

Aged↗

Urine and plasma catecholamine and cortisol concentrations after myocardial revascularization. Modulation by continuous sedation. Multicenter Study of Perioperative Ischemia (McSPI) Research Group, and the Ischemia Research and Education Foundation (IREF).

BACKGROUND: Cardiopulmonary bypass is associated with substantial release of catecholamines and cortisol for 12 or more h. A technique was assessed that may mitigate the responses with continuous 12-h postoperative sedation using propofol. METHODS: One hundred twenty-one patients having primary elective cardiopulmonary bypass graft (CABG) surgery were enrolled in a double-blind, randomized trial and anesthetized using a standardized sufentanil-midazolam regimen. When arriving at the intensive care unit (ICU), patients were randomly assigned to either group SC (standard care), in which intermittent bolus administration of midazolam and morphine were given as required to keep patients comfortable; or group CP (continuous propofol), in which 12 h of continuous postoperative infusion of propofol was titrated to keep patients deeply sedated. Serial perioperative measurements of plasma and urine cortisol, epinephrine, norepinephrine, and dopamine were obtained; heart rate and blood pressure were recorded continuously, and medication use, including requirements for opioids and vasoactive drugs, was recorded. Repeated-measures analysis was used to assess differences between study groups for plasma catecholamine and cortisol levels at each measurement time. RESULTS: In the control state-before the initiation of postoperative sedation in the ICU-no significant differences between study groups were observed for urine or plasma catecholamine or cortisol concentrations. During the ICU study period, for the first 6-8 h, significant differences were found between study groups SC and CP in plasma cortisol (SC = 28 +/- 15 mg/dl; CP = 19 +/- 12 mg/dl; estimated mean difference [EMD] = 9 mg/dl; P = 0.0004), plasma epinephrine (SC = 132 +/- 120 micrograms/ml; CP = 77 +/- 122 micrograms/ml; EMD = 69 micrograms/ml; P = 0.009), urine cortisol (SC = 216 +/- 313 micrograms/ml; CP = 93 +/- 129 micrograms/ml; EMD = 127 micrograms/ml; P = 0.007), urine dopamine (SC = 85 +/- 48 micrograms; CP = 52 +/- 43 micrograms; EMD = 32 micrograms; P = 0.002), urine epinephrine (SC = 7 +/- 8 micrograms; CP = 4 +/- 5 micrograms; EMD = 3 micrograms; P = 0.0009), and urine norepinephrine (SC = 24 +/- 14 mg; CP = 13 +/- 9 mg; EMD = 11 mg; P = 0.0004). Reductions in urine and plasma catecholamine and cortisol concentrations found for the CP group generally persisted during the 12-h propofol infusion period and then rapidly returned toward control (SC group) values after propofol was discontinued. Postoperative opioid use was reduced in the CP group (SC = 97%; CP = 49%; P = 0.001), as was the incidence of tachycardia (SC = 79%; CP = 60%; P = 0.04) and hypertension (SC = 58%; CP = 33%; P = 0.01), but the incidence of hypotension was increased (SC = 49%; CP = 81%; P = 0.001). CONCLUSIONS: Cardiopulmonary bypass graft surgery is associated with substantial increases in plasma and urine catecholamine and cortisol concentrations, which persist for 12 or more h. This hormonal response may be mitigated by a technique of intensive continuous 12-h postoperative sedation with propofol, which is associated with a decrease in tachycardia and hypertension and an increase in hypotension.

Aged↗

Human immunodeficiency virus-associated vasculopathy in transgenic mice.

There is substantial clinical evidence for the development of vascular disorders in human immunodeficiency virus (HIV)-infected individuals, particularly in the form of vasculitis. Transgenic mice carrying a replication-defective HIV-1 provirus with selective deletion of the gag, pol, and env genes developed extensive vasculopathy. Restricted expression of HIV nonstructural genes in smooth muscle cells was accompanied by the migration and proliferation of these cells in blood vessels of all sizes and at different body sites. The frequent infiltration observed in the hypertrophic vessel walls occurred predominantly in the adventitia and was composed of primarily T cells and occasionally plasma cells. The intimal thickening generated significant luminal narrowing in some vessels, and the restricted blood flow led to ischemia in the affected tissues. Interestingly, the endothelium did not appear to support HIV gene expression or be involved in the pathological process. This transgenic model provides an opportunity to dissect the mechanism underlying HIV-associated vasculopathy.

Animals↗

Extracellular deposition of beta-amyloid upon p53-dependent neuronal cell death in transgenic mice.

The finding that intracellular expression of the beta-amyloid protein (Abeta) under a neuron-specific promoter led progressively to degeneration and death of neurons in the brains of transgenic mice provides a unique opportunity to utilize this animal model to both understand the mechanism that underlies neuronal cell death and define the complexity of events which may ensue. We observed a correlation between Abeta accumulation in selective neurons and activation of p53, a protein that has been implicated in the induction of apoptosis. Histological and immunohistochemical evaluations of adjacent brain sections suggest that expression of p53 is accompanied by nuclear DNA fragmentation. In certain regions with marked neuronal cell death, extracellular deposition of A(beta) became evident, together with the local activation of astrocytes. Interestingly, the neuritic structures underlying the Abeta deposits showed altered synaptophysin immunoreactivity and morphologic evidence for damage. This transgenic mouse model suggests that intracellular generation of the Abeta protein not only leads to the death of the neuron but may also functionally impair neighboring neurons as well. It further offers a mechanism whereby neuritic plaques may be derived.

Alzheimer Disease↗

Second generation hybrid polar compounds are potent inducers of transformed cell differentiation.

Hybrid polar compounds, of which hexamethylenebisacetamide (HMBA) is the prototype, are potent inducers of differentiation of murine erythroleukemia (MEL) cells and a wide variety of other transformed cells. HMBA has been shown to induce differentiation of neoplastic cells in patients, but is not an adequate therapeutic agent because of dose-limiting toxicity. We report on a group of three potent second generation hybrid polar compounds, diethyl bis-(pentamethylene-N,N-dimethylcarboxamide) malonate (EMBA), suberoylanilide hydroxamic acid (SAHA), and m-carboxycinnamic acid bis-hydroxamide (CBHA) with optimal concentrations for inducing MEL cells of 0.4 mM, 2 microM, and 4 microM, respectively, compared to 5 mM for HMBA. All three agents induce accumulation of underphosphorylated pRB; increased levels of p2l protein, a prolongation of the initial G1 phase of the cell cycle; and accumulation of hemoglobin. However, based upon their effective concentrations, the cross-resistance or sensitivity of an HMBA-resistant MEL cell variant, and differences in c-myb expression during induction, these differentiation-inducing hybrid polar compounds can be grouped into two subsets, HMBA/EMBA and SAHA/CBHA. This classification may prove of value in selecting and planning prospective preclinical and clinical studies toward the treatment of cancer by differentiation therapy.

Acetamides↗

Application of exponential smoothing for nosocomial infection surveillance.

Detection of outbreaks of infection or increases in bacterial resistance to antimicrobial agents is an essential component of hospital infection control surveillance. The authors applied the method of exponential smoothing to microbiology data from 1987-1992 to investigate a suspected outbreak of gentamicin resistance among Pseudomonas aeruginosa bacteria at the Department of Veterans Affairs Medical Center, San Francisco, California, in 1991-1992. The years 1987-1990 were used to develop the baseline for the forecast model. Application of the model indicated that two observed prominent peaks in the annual cumulative incidence of gentamicin-resistant P. aeruginosa were within the upper bounds of their respective 95% confidence intervals as estimated by the forecast model--i.e., that no epidemic was in progress. This prediction was supported by investigations by the hospital's infection control team which indicated that the apparent increases were due to readmission of patients previously known to harbor these organisms. In contrast, application of a typically employed method that ignores the time series data structure indicated that there were 6 months in which incidence rates exceeded the upper bounds of their respective 95% confidence intervals, thereby erroneously suggesting that an epidemic was in progress. Recursive algorithms and some simplifying assumptions that do not affect the validity of inferences make the application of this method practical for nosocomial infection control programs.

Anti-Bacterial Agents↗

A knowledge-based model construction approach to medical decision making.

We present a framework for representing the probabilistic effects of actions and contingent treatment plans. Our language has a well-defined declarative semantics and we have developed an implemented algorithm (named BNG) that generates Bayesian networks (BN) to compute the posterior probabilities of queries. In this paper we address the problem of projecting a contingent treatment plan by automatically constructing a structure of interrelated BNs, which we call a BN-graph, and applying the available propagation procedures on it. To address the optimal plan generation, we base our approach on the observation that normally the target plan space has a well-defined structure. We provide a language to describe plan spaces which resembles a programming language with loops and conditionals. We briefly present the procedures for finding the optimal plan(s) from such specified plan spaces.

Acute Disease↗

Effect of older age on survival in human immunodeficiency virus (HIV) disease.

To evaluate the impact of older age (> 50 years old) on survival in late-stage human immunodeficiency virus (HIV) disease, the authors analyzed 846 HIV-infected patients at the San Francisco Veterans Affairs Medical Center from 1987 to 1992. The median age was 42 years with 171 (20.2%) subjects aged 50 or more years. Survival was measured from the date of initial lymphocyte testing (median CD4 count, 223 cells/mm3) until death or censoring. Compared with those aged less than 40 years, and after multivariate proportional hazards adjustment for other significant determinants of survival (CD4 percentage, CD8 count, hematocrit, and prior acquired immunodeficiency syndrome diagnosis), there was no difference in survival for those aged 40-49 years, but there was a trend toward decreased survival in those aged 50-59 years (relative hazard = 1.32, 95% confidence interval 0.90-1.94) and in those aged 60 or more years (relative hazard = 1.56, 95% confidence interval 0.99-2.46). The impact of older age on mortality in HIV disease is, however, less than the impact of age on overall mortality in the United States. Accordingly, while older HIV-infected patients do have a somewhat poorer survival, this risk need not be too highly emphasized in individual patients; older patients deserve aggressive management.

Adult↗

Gain of function mutations for paralogous Hox genes: implications for the evolution of Hox gene function.

To investigate the functions of paralogous Hox genes, we compared the phenotypic consequences of altering the embryonic patterns of expression of Hoxb-8 and Hoxc-8 in transgenic mice. A comparison of the phenotypic consequences of altered expression of the two paralogs in the axial skeletons of newborns revealed an array of common transformations as well as morphological changes unique to each gene. Divergence of function of the two paralogs was clearly evident in costal derivatives, where increased expression of the two genes affected opposite ends of the ribs. Many of the morphological consequences of expanding the mesodermal domain and magnitude of expression of either gene were atavistic, inducing the transformation of axial skeletal structures from a modern to an earlier evolutionary form. We propose that regional specialization of the vertebral column has been driven by regionalization of Hox gene function and that a major aspect of this evolutionary progression may have been restriction of Hox gene expression.

Animals↗

Relationship between an index of tidal flow and lower respiratory illness in the first year of life.

The ratio of time to tidal peak flow (Tme) to total tidal expiratory time (Te) has been reported to be decreased in infants who later develop wheezing lower respiratory tract illness (LRI) in the first year of life. The relationship between Tme/Te to the subsequent occurrence of LRI was studied in 98 infants in whom the first measurement of pulmonary function (PFT) was made before the age of 6 months and before the occurrence of any LRI. Occurrence of LRI was evaluated by standardized questionnaires at well-baby visits, through biweekly telephone calls to mothers, and review of all visits to physicians. Tme/Te was derived from 10 tidal breathing loops during stable respiration. Partial expiratory flow-volume curves were obtained with the rapid compression technique, and passive respiratory mechanics were evaluated by the single breath occlusion technique. Analysis of Tme/Te was stratified by age (< or = 10 weeks, > 10 weeks to 6 months) to take into account the age-related decline in Tme/Te. Among 80 infants first tested at < or = 10 weeks, Tme/Te was 12.4% shorter in those who developed a LRI vs. those who did not (P = 0.46); for 18 infants tested after 10 weeks, the difference was 1.9% (P = 0.39). Among male infants, the decrease in Tme/Te was observed only for those studied at < or = 10 weeks (16%, P = 0.16). For females, decreases were observed for those tested at < or = 10 weeks (11%, P = 0.83) and those tested after 10 weeks (17.5%, P = 0.09). Poisson regression analysis which included data for multiple measurements of Tme/Te over the first year of life and adjusted for age-at-test and maternal smoking during pregnancy also demonstrated a greater decrease in Tme/Te in female infants who subsequently develop an LRI (P = 0.08). Level of Tme/Te was not consistently related to level of respiratory system resistance (RRS) or flow at functional residual capacity (VFRC). Level of VFRC has been shown previously to be related to the occurrence of LRI and in this study to RRS(P = 0.007). The results indicate (1) a shortened Tme/Te is only weakly associated with the development of LRI in the first year of life; (2) this ratio is a less precise and an epidemiologically less useful measure than is VFRC to investigate groups of infants with and without LRI and without clinically significant underlying lung disease.

Age Factors↗

Functional inactivation but not structural mutation of p53 causes liver cancer.

Structural mutations in the p53 gene are seen in virtually every form of human cancer. To determine whether such mutations are important for initiating tumorigenesis, we have been studying hepatocellular carcinoma, in which most cases are associated with chronic hepatitis B virus infections. Using a transgenic mouse model where expression of a single HBV gene product, the HBx protein, induces progressive changes in the liver, we show that tumour development correlates precisely with p53 binding to HBx in the cytoplasm and complete blockage of p53 entry into the nucleus. Analysis of tumour cell DNA shows no evidence for p53 mutation, except in advanced tumours where a small proportion of cells may have acquired specific base substitutions. Our results suggest that genetic changes in p53 are late events which may contribute to tumour progression.

Animals↗

Maternal smoking during pregnancy. Effects on lung function during the first 18 months of life.

The present investigation evaluated the effects of maternal smoking during pregnancy on the growth of lung function during the first 18 mo of life in 159 infants who were part of a longitudinal study of the effects of maternal smoking on respiratory health. Infant pulmonary function was assessed at 2 to 6 wk of age and at 4 to 6, 9 to 12, and 15 to 18 mo of age by partial expiratory flow-volume curves and helium dilution FRC. Maternal smoking was assessed by standard questionnaire and urine cotinine measurements. Maternal smoking during pregnancy was associated with a reduction of 9.4 +/- 4.3 ml (p = 0.029) for FRC and 33 +/- 12.3 ml/s (p = 0.008) reduction for flow at FRC (VFRC) after controlling for the effects of growth (length). The effect of maternal smoking was greater for female infants than for male infants. At 1 yr female infants exposed in utero were predicted to have a 16% reduction in VFRC compared with 5% for male infants. No sex difference was seen for FRC or VFRC/FRC. Exposure to environmental tobacco smoke in the postnatal period was not significantly related to reduced FRC or VFRC. These data provide further evidence that maternal smoking during pregnancy may play a greater role than postnatal and childhood exposure on the observed effects on lung function in children.

Female↗

Clinical simulation using context-sensitive temporal probability models.

We present a language for representing context-sensitive temporal probabilistic knowledge. Context constraints allow inference to be focused on only the relevant portions of the probabilistic knowledge. We provide a declarative semantics for our language and an implemented algorithm (BNG) that generates Bayesian networks to compute the posterior probabilities of queries. We illustrate the use of the BNG system by applying it to the problem of modeling the effects of medications and other interventions on the condition of a patient in cardiac arrest.

Artificial Intelligence↗

Factors associated with survival in human immunodeficiency virus-infected patients with very low CD4 counts.

The authors examined the survival experience of 289 human immunodeficiency virus (HIV)-infected men to identify factors independently associated with survival in patients with very low CD4 counts (< or = 100/mm3). All subjects were HIV-infected men cared for at the San Francisco Veterans' Affairs Medical Center between January 1988 and November 1991. Survival was measured from the date on which a patient was first known to have a CD4 count < or = 100/mm3 until death or censoring. Factors potentially associated with survival were examined initially using the product limit (Kaplan-Meier) method; a multivariate model of survival was constructed using a proportional hazards (Cox) regression. Four variables were identified as independently associated with survival (p < 0.05) in the Cox proportional hazards model: CD4 count, hematocrit, azidothymidine use, and clinical stage (prior history of acquired immunodeficiency syndrome vs. no prior history). All 16 possible combinations of these four (dichotomized) variables were examined; eight different patterns of survival were detected. Identification of survival patterns that can be described by data obtained as part of routine clinical care has implications for patient care, the design of clinical trials, the study of mechanisms of progression of HIV-related immunosuppression, and planning of health care resource needs for populations of patients with very low CD4 counts.

Adult↗

V-sis induces Egr-1 expression by a pathway mediated by c-Ha-Ras.

The early growth response gene, Egr-1, is up-regulated transiently by mitogens and many other stimuli in all cells tested. Using NIH3T3 cells conditionally expressing v-sis from a metallothionein promoter, we show that the addition of Zn2+ stimulates the production of PDGF-B (v-sis) and elicits the expression of Egr-1 in a dose-dependent and time-regulated manner. The signal is likely independent of protein kinase C, but depends on tyrosine kinase and other kinase activities and is mediated by c-Ha-Ras since the presence of dominant-negative mutants of Ras and Raf abrogates the induction of Egr-1 expression by Zn2+. Transiently activated Ras expression in NIH3T3 cells also stimulates the transient expression of Egr-1, but cells that constitutively express Ras do not have elevated levels of Egr-1. Transient assays also demonstrated that Zn2+ or activated Ras expression stimulate the activity of a 950 bp Egr-1 promoter-reporter gene construct and this is abrogated in the presence of mutant Ras and Raf. The accumulated data show that Egr-1 gene expression is regulated by multiple mechanisms, as would be needed for putative roles in cell proliferation, in suppression of transformation and in differentiation.

3T3 Cells↗

Effects of nitric acid gas alone or in combination with ozone on healthy volunteers.

Nitric acid (HNO3) is the most prevalent acid air pollutant in the western United States and has the potential to cause adverse respiratory effects through both acidification and oxidation reactions. To study this potential, we measured physiologic (specific airway resistance, SRaw, FEV1, and FVC) and bronchoalveolar lavage (total and differential cell counts, LDH, fibronectin, and total protein) end points in a group of 10 healthy, athletic subjects who were exposed to 500 micrograms/m3 of HNO3 gas or filtered air for 4 h during moderate exercise (ventilatory rate, 40 L/min) and underwent bronchoscopy 18 h later. Under an identical protocol, 10 healthy subjects were exposed to 500 micrograms/m3 of HNO3 gas plus 0.20 ppm ozone (O3) or 0.20 ppm O3 alone to determine if HNO3 might enhance the toxicity of O3. In addition to bronchoalveolar lavage (BAL), we employed the techniques of isolated left mainstem bronchial lavage and bronchial biopsy to determine if proximal airway injury was caused by pollutant exposure and whether there was any correlation with the degree of distal lung injury as assessed by BAL. We found no significant differences in pulmonary function tests or in the cellular or biochemical constituents in either the BAL or the left mainstem lavage fluids between the HNO3 and the air exposures. Similarly, there were no differences in these end points between the HNO3/O3 and the O3 exposures. Furthermore, there were no significant differences in the bronchial biopsy specimens between the HNO3 and air exposures or between the HNO3/O3 and O3 exposures.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗